University of Miami School of Medicine, United States.
University of California, San Francisco School of Nursing, United States.
Brain Behav Immun. 2018 Jul;71:108-115. doi: 10.1016/j.bbi.2018.04.004. Epub 2018 Apr 18.
Stimulant use may accelerate HIV disease progression through biological and behavioral pathways. However, scant research with treated HIV-positive persons has examined stimulant-associated alterations in pathophysiologic processes relevant to HIV pathogenesis. In a sample of 55 HIV-positive, methamphetamine-using sexual minority men with a viral load less than 200 copies/mL, we conducted RNA sequencing to examine patterns of leukocyte gene expression in participants who had a urine sample that was reactive for stimulants (n = 27) as compared to those who tested non-reactive (n = 28). Results indicated differential expression of 32 genes and perturbation of 168 pathways in recent stimulant users. We observed statistically significant differential expression of single genes previously associated with HIV latency, cell cycle regulation, and immune activation in recent stimulant users (false discovery rate p < 0.10). Pathway analyses indicated enrichment for genes associated with inflammation, innate immune activation, neuroendocrine hormone regulation, and neurotransmitter synthesis. Recent stimulant users displayed concurrent elevations in plasma levels of tumor necrosis factor - alpha (TNF-α) but not interleukin 6 (IL-6). Further research is needed to examine the bio-behavioral mechanisms whereby stimulant use may contribute to HIV persistence and disease progression.
兴奋剂的使用可能通过生物和行为途径加速 HIV 疾病的进展。然而，针对接受治疗的 HIV 阳性人群，很少有研究检查过与 HIV 发病机制相关的生理过程中与兴奋剂相关的改变。在一项研究中，55 名 HIV 阳性、使用冰毒的性少数男性，病毒载量小于 200 拷贝/ml，我们进行了 RNA 测序，以检测尿液样本中兴奋剂呈阳性（n=27）和呈阴性（n=28）的参与者白细胞基因表达模式。结果表明，在最近使用兴奋剂的人群中，有 32 个基因的表达存在差异，168 个通路受到干扰。我们观察到最近使用兴奋剂的人群中，与 HIV 潜伏期、细胞周期调节和免疫激活相关的单个基因的表达存在统计学上显著差异（错误发现率 p < 0.10）。通路分析表明，与炎症、先天免疫激活、神经内分泌激素调节和神经递质合成相关的基因富集。最近使用兴奋剂的人群的肿瘤坏死因子-α（TNF-α）水平升高，但白细胞介素 6（IL-6）水平没有升高。需要进一步研究生物行为机制，以了解兴奋剂使用如何导致 HIV 持续存在和疾病进展。
